[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Cell injury, adaptation and death](https://durgical.com/en/general-pathology/#a-injury) › Mechanisms of cell injury: ATP, mitochondria, calcium, membranes and DNA [General pathology](https://durgical.com/en/general-pathology/) · [Cell injury, adaptation and death](https://durgical.com/en/general-pathology/#a-injury) # Mechanisms of cell injury: ATP, mitochondria, calcium, membranes and DNA - Mechanism Most injuries act through a few shared paths: energy loss, broken mitochondria, excess calcium, free radicals, leaky membranes and DNA damage. Updated 2026-11-01 ## Key points - ATP depletion: pump failure, swelling, anaerobic glycolysis with lactic acidosis, and less protein synthesis. - Mitochondrial damage opens the permeability transition pore and releases cytochrome c (apoptosis). - Cytosolic calcium activates phospholipases, proteases, endonucleases and ATPases. - Membrane damage of mitochondria, lysosomes and the plasma membrane is the final common event of necrosis. - Unrepaired DNA damage activates p53, which halts the cycle or triggers apoptosis. ## What it is Different injuries meet in a small set of biochemical routes. Loss of ATP stops pumps and synthesis; damaged mitochondria release death signals; excess cytosolic calcium switches on destructive enzymes; free radicals oxidize lipids, proteins and DNA; and damaged membranes let the cell leak. When DNA or proteins are damaged beyond repair, the cell usually chooses apoptosis. ## Function - ATP depletion: the Na⁺/K⁺ and Ca²⁺ pumps fail, the cell swells and calcium rises inside it. - Mitochondrial injury: less ATP, more free radicals, and leak of pro-apoptotic proteins. - Calcium overload: enzymes digest membranes, proteins and chromatin; more mitochondrial pores open. - Oxidative stress: free radicals peroxidize membrane lipids and break DNA. - Membrane damage: loss of the ion barrier, release of lysosomal enzymes and leak of cell contents. - DNA and protein damage: p53 or the unfolded protein response push the cell toward apoptosis. ## Step by step - An insult (hypoxia, toxin, radiation, infection) hits one or more cell targets. - ATP falls as oxidative phosphorylation fails; pumps stop and the cell swells. - Calcium floods the cytosol from outside and from the ER and mitochondria. - Calcium-activated enzymes and free radicals damage membranes, proteins and DNA. - Mitochondria lose their membrane potential and release cytochrome c. - Mild damage leads to apoptosis; massive damage with membrane rupture leads to necrosis. ## Clinical notes - Cyanide blocks cytochrome c oxidase (complex IV): cells cannot use oxygen and the venous blood stays bright red. - Inherited mitochondrial diseases (MELAS, Leigh syndrome) hurt organs with high energy needs: brain, muscle and heart. ## Memory aid Energy, power plant, calcium, sparks, walls and blueprint: ATP, mitochondria, calcium, free radicals, membranes and DNA. ## Test yourself Think of the answer, then tap the question to see it. ## Which enzymes does an increase in cytosolic calcium activate? Phospholipases, proteases, endonucleases and ATPases, which damage membranes, the cytoskeleton, chromatin and further deplete ATP. ## Why does anaerobic glycolysis during ischemia lead to chromatin clumping? It produces lactic acid and lowers the intracellular pH, which causes the nuclear chromatin to clump. ## What does a cell usually do when its DNA damage cannot be repaired? p53 accumulates, arrests the cell cycle and, if repair fails, triggers apoptosis by the intrinsic pathway. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/mechanisms-of-cell-injury-atp-mitochondria-calcium-membranes-and-dna/) ## Related - [Reversible vs irreversible cell injury: the point of no return](https://durgical.com/en/general-pathology/reversible-vs-irreversible-cell-injury-the-point-of-no-return/) - [Oxidative stress and free-radical injury](https://durgical.com/en/general-pathology/oxidative-stress-and-free-radical-injury/) - [Hypoxia, ischemia and reperfusion injury](https://durgical.com/en/general-pathology/hypoxia-ischemia-and-reperfusion-injury/) - [Apoptosis: the intrinsic and extrinsic pathways](https://durgical.com/en/general-pathology/apoptosis-the-intrinsic-and-extrinsic-pathways/) - [Endoplasmic reticulum stress and the unfolded protein response](https://durgical.com/en/general-pathology/endoplasmic-reticulum-stress-and-the-unfolded-protein-response/) ## Related conditions - [Myocardial Infarction (Heart Attack)](https://durgical.com/en/conditions/myocardial-infarction/) - [Ischaemic stroke](https://durgical.com/en/conditions/ischaemic-stroke/) - [Cyanide poisoning](https://durgical.com/en/conditions/cyanide-poisoning/) - [Carbon monoxide poisoning](https://durgical.com/en/conditions/carbon-monoxide-poisoning/) - [MELAS (mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes)](https://durgical.com/en/conditions/melas/) - [Leigh syndrome](https://durgical.com/en/conditions/leigh-syndrome/) - [Leber hereditary optic neuropathy (LHON)](https://durgical.com/en/conditions/leber-hereditary-optic-neuropathy/) - [Acute kidney injury](https://durgical.com/en/conditions/acute-kidney-injury/) - [Malignant hyperthermia](https://durgical.com/en/conditions/malignant-hyperthermia/) ## Elsewhere in DurgiPedia - [Electron transport chain and oxidative phosphorylation](https://durgical.com/en/biochemistry/pathways/electron-transport-chain-and-oxidative-phosphorylation/) - [IP₃, DAG and calcium pathway](https://durgical.com/en/biochemistry/topics/ip-dag-and-calcium-pathway/) - [Na⁺/K⁺-ATPase (sodium pump)](https://durgical.com/en/biochemistry/enzymes/na-k-atpase/) - [Cytochrome c](https://durgical.com/en/biochemistry/enzymes/cytochrome-c/) - [ATP (adenosine triphosphate)](https://durgical.com/en/biochemistry/molecules/atp/) - [Cell volume regulation](https://durgical.com/en/physiology/cell-volume-regulation/) - [Organelles: nucleus, ER, Golgi, mitochondria, lysosomes, peroxisomes](https://durgical.com/en/histology/organelles-nucleus-er-golgi-mitochondria-lysosomes-peroxisomes/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [What is a cell?: MedlinePlus Genetics](https://medlineplus.gov/genetics/understanding/basics/cell/) (MedlinePlus, US National Library of Medicine, 2024); [Mitochondrial Diseases: MedlinePlus](https://medlineplus.gov/mitochondrialdiseases.html) (MedlinePlus, US National Library of Medicine, 2024); [Carbon monoxide poisoning: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/002804.htm) (MedlinePlus, US National Library of Medicine, 2024). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/mechanisms-of-cell-injury-atp-mitochondria-calcium-membranes-and-dna/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/mechanisms-of-cell-injury-atp-mitochondria-calcium-membranes-and-dna/